The major goal of this research project is to understand the biochemical, physiological and evolutionary roles of mitochondrial RNA polymerase in normal and neoplastic tissues. A procedure has been developed for the solubilization and partial purification of DNA-dependent RNA polymerase, devoid of homopolymer-forming enzyme system, from rat liver mitochondria. The enzyme will be purified extensively. The properties and subunicomposition of the enzyme will be compared with those of nuclear and bacterial RNA polymerases. The effect of hormones, particularly of those exerting a stimulatory effect on RNA polymerase activity, prior to any nuclear changes, at a low and physiological dose, on the mitochondrial RNA polymerase will be studied using purified enzyme and exogenous mitochondrial DNA template. The effect of various inhibitors and templates on the enzyme activity will also be investigated. Concurrently, RNA polymerase from several types of tumors will be isolated and purified. Structural differences between normal and malignant enzymes will be determined. The effect of various compounds upon the enzyme will be tested in an effort to restore normal growth conditions in tumors by modifying the RNA synthesizing system of their mitochondria.